Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lacting rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lacting rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolacting during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.
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PMID:Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat. 689 86

Under influence of the ultraviolet radiation the formerly lowered 25-hydroxycholecalciferol (25-OH-CC) level increases in persons with healthy kidneys. Such investigations were not yet carried out in patients undergoing dialysis. Since the insufficiency of active vitamin-D-metabolites plays an essential role in the development of the renal osteopathy, since 1978 in 13 patients undergoing dialysis a regular ultraviolet radiation has been performed, in order to stimulate the cutaneous vitamin-D-production. The time of observation was 31.7 +/- 14.3 months. Deionized water served for the production of dialysate. The calcium content was about 3.5 +/- 3.8 mval/l. The patients had very rarely bone and joint complaints. Severe clinical complications of renal osteopathy developed only in one female patient in the 3rd year of dialysis with a fracture of the neck of the femur as well as in a 2nd patient after transplantation of a kidney with permanently progressing demineralization and spondylitis. Controls of the courses showed only in 18.2% a progressing loss of the peripheral mineral content of the bones. The alkaline phosphatase was not increased, the alkaline bone phosphatase appeared with low and not provable activities. A suppression of the secondary hyperparathyroidism could not be proved. Parathormone was increased with 2.30 +/- 1.90 micrograms/l. The 25-OH-CC-levels were normal or slightly increased with 39.1 +/- 12.4 micrograms/l, whereas they were essentially lower in a comparative group without ultraviolet radiation. Therefore in connection with the very low rate of complications of the renal osteopathy with normalized 25-OH-CC-levels new therapeutic possibilities were the result in patients undergoing dialysis after ultraviolet radiation. The increasing importance consists also in the fact that 90% of the human vitamin-D-need are supplied via skin and it was proved by animal experiments that also after bilateral nephrectomy the formation of the active vitamin-D-metabolite 1,25-dihydroxycholecalciferol is possible by photosynthesis.
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PMID:[Effect of ultraviolet irradiation on renal osteopathy in patients in the chronic hemodialysis program]. 716 24

The relationship between bone formation and vitamin D metabolism was investigated in the developing chick embryo. Fertilized White Leghorn eggs were incubated at 38 degrees C in an incubator for 21 days. The fresh weight and calcium content of embryonic tibiae began to increase at day 12 and attained maximal values at day 19. Bone alkaline phosphatase and citrate decarboxylation activities, both of which represent osteoblastic activity, also began to increase at days 10-12, reached maximal values at day 19 and sharply declined thereafter. Both bone enzyme activities were highly correlated with CA2+-binding activity in the chorioallantoic membrane measured by the Chelex 100 assay. When mesonephric and metanephric homogenates were incubated with 25-hydroxy[3H]cholecalciferol, a marked and concomitant increase occurred in the metanephric 1 alpha- and 24-hydroxylase activity after day 14. The production of 1 alpha, 25-dihydroxycholecalciferol attained a maximal value at day 19 and decreased thereafter, whereas that of 24,25-dihydroxycholecalciferol continued to increase until hatching. The production rate of 1 alpha, 25-dihydroxycholecalciferol by the metanephros coincided with the changes in Ca2+-binding activity in the chorioallantoic membrane and osteoblastic activity. Since both intestinal calcium absorption and bone mineral mobilization do not occur in embryonic life, these results support the idea that 1 alpha, 25-dihydroxycholecalciferol may be involved directly in bone formation or induction of a calcium-binding protein in the chorioallantoic membrane.
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PMID:Vitamin D metabolism and its possible role in the developing chick embryo. 730 73

Clinically asymptomatic patients undergoing hemodialysis and with histologically proven renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25[OH]2D3) or with placebo for 9-37 weeks. Serum concentrations of total calcium were frequently increased when the ionized calcium was raised into the normal range. Serum magnesium was in the upper normal range due to the presence of magnesium in the aluminum hydroxide used to lower the hyperphosphatemia, which was difficult to control. Basal serum parathyroid hormone (PTH) levels were increased and seven times higher when measured with a radioimmunoassay recognizing mainly COOH-terminal fragments of human PTH-(1-84) (C-terminal assay) as compared to another assay measuring predominantly intact PTH-(1-84) (N-terminal assay). During treatment with 1,25 (OH)2D3, serum PTH returned towards the normal range with increasing calcium levels. Mean PTH concentrations decreased significantly by 34% (p less than 0.05) when measured with the N-terminal assay and by only 14% (p greater than 0.1) in the C-terminal assay. Serum alkaline phosphatase activity and the mineral content of the forearm estimated by photon absorptiometry remained unchanged.
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PMID:1,25-Dihydroxycholecalciferol in dialysed patients with clinically asymptomatic renal osteodystrophy. A controlled study. 735 81

Pseudohypoparathyroidism (PHP) is a condition characterized by hypocalcemia, hyperphosphatemia, and an impaired phosphaturic response to exogenous parathormone (PTH). A minority of patients with PHP have associated bone disease, and in some the radiological appearances have been suggestive of rickets. We report a patient with PHP who had epiphyseal enlargement and bowing of the long bones similar to that seen in rickets. Radiology showed generalized osteomalacia with failure of epiphyseal calcification and several pseudofractures. Bone biopsy showed increased osteoid seams. The phalanges of both hands showed subperiosteal erosions consistent with hyperparathyroidism. Biochemically, he had persistent hypocalcemia, hyperphosphatemia, and an elevated alkaline phosphatase. Plasma calcitonin, magnesium, and 25-hydroxycholecalciferol levels were normal. The 1,25-dihydroxycholecalciferol level was within the normal adult range but was probably inappropriately low for an adolescent. Plasma parathormone was elevated (1.3--1.7 microgram/liter; normal, < 0.73). His diet was not deficient in vitamin D. Gastrointestinal function was normal. Renal function was normal, apart from an increase in the maximum tubular reabsorption of phosphate (46--52.6 mg/liter glomerular filtration rate; normal, 38 +/- 5). Intravenous PTH infusion tests were performed on the patient and a control subject before and 6 months after serum calcium levels had returned to normal. The maximum increases in cAMP excretion in the patient were 0.03 and 0.05 mmol/g creatinine before and after treatment, respectively (control, 0.53 and 0.24); the maximum increases in phosphate excretion in the patient were 0.14 and 0.04 mmol/g creatinine before and after treatment, respectively (control, 0.32 and 0.07). He responded to initial treatment with a high dose of calciferol and later to 1,25-dihydroxycholecalciferol in a dose of 1 microgram/day. It is considered that renal resistance to PTH is his primary abnormality, with the bone disease representing a secondary phenomenon.
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PMID:Pseudohypoparathyroidism presenting with rickets. 741 91

We prospectively studied the long-term effects of intravenous calcitriol in 17 hemodialysis patients with severe secondary hyperparathyroidism (HPT) for 25.7 +/- 3.4 (+/- SE) months. Calcitriol was given thrice weekly after dialysis. Subsequently, changes were made every 3-4 weeks based upon serum chemistries. Total calcium and inorganic phosphorus were measured weekly; alkaline phosphatase (AP) and IRMA-PTH were measured monthly. Inorganic phosphate was controlled with calcium supplements. With calcitriol therapy both IRMA-PTH and AP decreased from 876 +/- 113 to 65 +/- 13 pg/ml (p < or = 0.001) and 432 +/- 106 to 103 +/- 15 U/ml (p < or = 0.001), respectively. Each patient had a reduction in IRMA-PTH and AP. Nadir IRMA-PTH occurred at 55.4 +/- 7.3 weeks. The maximum and mean maximum doses of calcitriol were 8.0 and 4.1 +/- 0.4 micrograms thrice weekly, respectively. Hypercalcemia tended to occur in those patients who were hypercalcemic prior to the initiation of intravenous calcitriol therapy. All hypercalcemic episodes were asymptomatic and reversed either by temporary withdrawal or lowering of the calcitriol dose. Hyperphosphatemia developed in those patients with a history of elevated serum phosphates and was mostly related to dietary and medication noncompliance. We conclude that intravenous calcitriol was uniformly effective and safe for the long-term therapy of severe HPT in ESRD. Careful attention to serum phosphate control is required.
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PMID:Long-term high dose intravenous calcitriol therapy in end-stage renal disease patients with severe secondary hyperparathyroidism. 763 48

1 alpha,25-Dihydroxyvitamin D3 (D3), T3, and retinoids are necessary for normal skeletal development, and their actions are interdependent due to the heterodimerization capabilities of their receptors. We investigated the hypothesis that these hormones act on osteoblasts directly to produce complex target gene responses resulting from multiple hormone interactions. Physiological interactions among D3, T3, and retinoid signaling were analyzed in serum-free cultures of the osteosarcoma cell lines ROS 25/1, UMR106, and ROS 17/2.8. These cells express distinct stages of the osteoblast phenotype and coexpress appropriate hormone receptors. Regulation of collagen I alpha 1 and alpha 2, alkaline phosphatase, osteopontin, and osteocalcin messenger RNAs was dependent on the dose and duration of hormone stimulation and modified by cell confluence. Retinoids were required for comprehensive expression of phenotypic responses to D3 and T3 in each cell type and hormone interactions were both cell and target gene specific. Differing responses of target genes in each cell line may provide a molecular basis for discrete hormone actions seen at specific stages of osteoblast differentiation or skeletal development.
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PMID:Retinoids modify regulation of endogenous gene expression by vitamin D3 and thyroid hormone in three osteosarcoma cell lines. 766 49

Intravenous calcitriol is generally considered to be more efficient than oral administration in the treatment of secondary hyperparathyroidism of chronic renal failure, although a comparative and prospective study employing the same doses and modality of drug administration is lacking. We therefore evaluated 12 hemodialysis (HD) patients (51.7 +/- 9.4 years, mean +/- SD, HD for 8.7 +/- 4.7 years) with marked secondary hyperparathyroidism. Based on basal humoral and bone histologic parameters, we divided these patients into 2 comparable groups. Calcitriol (0.015 micrograms/kg) was given at the end of each dialysis intravenously in group A and orally in group B. Humoral parameters were evaluated basally and after 1, 2, 4 and 8 months. Ax bone biopsy was taken at the start and at the end of the study. From the first month of treatment, group A showed an increment in ionized calcium (from 1.28 +/- 0.08 to 1.37 +/- 0.12 mmol/l, p < 0.01), with a reduction in intact parathyroid hormone (from 470.1 +/- 349.5 to 255.5 +/- 256.5 pg/ml; p < 0.0003) and alkaline phosphatase (from 615.1 +/- 696.3 to 445.3 +/- 577.7 mU/ml, p < 0.001). The occurrence of hypercalcemia prompted a reduction in dialysate calcium content in 4 of 6 patients after 4 months, and of the calcitriol dose in 2 of 4 patients after 6 months. Ionized calcium then turned to 1.32 +/- 0.11 (p = n.s. compared to basal) while the intact parathyroid hormone concentration tended to revert (363.3 +/- 360 pg/ml, p = n.s. compared to basal) and alkaline phosphatase remained low (420 +/- 638 mU/ml, p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous versus oral calcitriol therapy in renal osteodystrophy: results of a prospective, pulsed and dose-comparable study. 781

Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 microns2/mm2/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis.
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PMID:Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. 786 12

The association of connate, left-sided, extensive epidermal verrucous nevus, multiple isolated bone tumors and vitamin-D-resistant rickets since childhood seen in a 20-year-old male patient corresponded to an epidermal nevus syndrome (ENS). However, other organ involvement occasionally associated with ENS could not be found in this patient, and his intraosseous tumors represented histologically benign hemangiomas. Serum analysis revealed hypophosphatemia (together with phosphaturia), decreased levels of 1,25-dihydroxycholecalciferol and elevated levels of alkaline phosphatase indicating hypophosphatemic osteomalacia. Therefore we suppose that vitamin-D-resistant rickets combined with skeletal tumors represents a peculiar type of osteomalacia caused by unilateral mesenchymomas.
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PMID:Extensive linear epidermal nevus associated with hemangiomas of bones and vitamin-D-resistant rickets. 794 84


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